Repairing a damaged heart remains a major challenge since the human heart has only a limited capacity to regenerate itself and damage to the heart muscle usually results in irreversible cardiac dysfunction. Much research is ongoing to develop technologies that may allow the refurbishing of failing myocardium with new muscle. Many of the existing cardiac tissue constructs used for in vitro models are in the form of tissue strips or patches. These tissue strips and patches can be used to measure contractile force, but cannot directly generate the types of measures that cardiologists are trained to understand, such as volume, pressure, ejection fraction, and stroke work. More recently, techniques have been developed to produce cardiac tissue chambers (organoids) that can generate these types of measures, and these newer techniques require a number of complex steps.
For instance, techniques for creating a cardiac organoid typically require 1) introducing a cold cell-matrix solution into a an outer cup-shaped mold; 2) inflating a balloon catheter in the cell-matrix solution to a desired chamber size to form the inner mold boundary; 3) placing a small ring above the balloon contacting the cell-matrix solution to prevent tissue slippage during culture; 4) removing the outer cup-shaped mold after a specified time period, such as 24 hours; 5) incubating the remaining cell-matrix solution with the balloon catheter for a specified time period, such as 7 to 10 days, during which the engineered cardiac tissue (organoid) would form a coordinated network compacted around the balloon; 6) carefully deflating the balloon and removing the organoid from the deflated balloon catheter following the incubation period; and 7) connecting the organoid to an isolated heart setup by suturing it to a fluid-filled cannula.
While these newer techniques have been effective in generating the types of measures that are important for cardiologists in evaluating the efficacy of the engineered cardiac tissue, they require the investigators to be very delicate with the organoid when removing the balloon catheter and suturing the organoid to the cannula so as to avoid damaging or compromising the structure of the organoid.